Tissue engineering of the right heart outflow tract by a biofunctionalized bioresorbable polymeric valved tube

TEH-TUBE

Project timeline

Start:
January 2014

Duration:
48 months

End:
December 2017

General Information

Approximately 42% of infants’ mortality in the world is related to congenital heart defects. Over 1/3 require the reconstruction of the right ventricular outflow tract by surgical procedures which currently use inert materials without any growth potential. Consequently, multiple reoperations are often required, with their attendant high risk of mortality and morbidity. The TEH-TUBE project will address these limitations by creating a novel bioabsorbable biomaterial using a polymeric valved tube either seeded with autologous adipose tissue derived stem cells (ADSC) or functionalized by a peptidic sequence triggering homing of the host cells onto the scaffold to make it a living self-populated structure. Key objectives of the project are: 1) Compare 3 different polymers processed by electrospinning to generate a competent valved tube; 2) Compare, in the selected polymer, ADSC seeding and peptide grafting using in vitro mechanical and biological tests as well as in vivo animal experiments; 3) Validate the ultimate combination (polymer + cells or peptides) in a clinically relevant large animal model (in this case, the growing lamb to specifically assess the regenerative and growth potential of the composite construct). This stepwise approach will be conducted within a tightly controlled regulatory framework to ensure that the final product meets the current ATMP (Advanced Therapy Medicinal Product) requirements for phase I/II clinical studies and, if successful, ultimate commercialization. The TEH-TUBE project aims at developing an innovative biomaterial for the treatment of congenital heart abnormalities in children and young adults. HZG will lead the work package on polymer biofunctionalization.